2. Synthesis of Oxazole
1. Reductive acetylation of α-oximino derivative of a ketone gives α-acylamino carbonyl
compound, which is refluxed with acid or phosphorous pentoxide. This involves dehydrative
cyclization.
2. By heating ethyl α-hydroxy ketosuccinate with formamide followed by hydrolysis and
decarboxylation.
H5C6
O
NOH Zn - CH3COOH
(CH3CO)2O
NH
H5C6
O
CH3
O
H+
N
O
HO CH3
H5C6
N
O CH3
H5C6
2- methyl- 5 -phenyl oxazole
-H2O
alpha-acyamino
carbonyl compound
alpha-oximino
derivative
COOC 2H5
C
CHOH
COOC 2H5
O
+ HCONH 2
N
O
H5C2OOC
H5C2OOC
Diethyloxazole- 4 , 5-
dicarboxylic acid
Ba(OH)2/H2O
Quinidine, Cu
N
O
Oxazole
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3. 3. By the interaction of acid imides and α-halogenoketones.
O
BrH2C
H5C6
+ C6H5
H2N
O
alpha-bromo
acetophenone
Benzamide
OH
BrHC
H5C6
+ C6H5
HN
HO
N
O C6H5
H5C6
2, 4-diphenyloxazole
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5. 1. Reaction with concentrated acids
Oxazoles are basic compounds, they can be decomposed by means of concentrated
acids.
2. Electrophilic substitution: Preferred attack is at position-5. These reactions occur
more readily when the oxazole ring is activated by electron-donating group. Oxazole is
more reactive with electrophiles than Thiazole but less than Imidazole.
N
O C6H5
H5C6
HCl
180 °C
(C6H5COCH 2NH3)Cl + C6H5COOH
+
2, 5-diphenyloxazole
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6. a. Bromination: Bromination of 2-phenyloxazole with N-bromosuccinimide gives
5-bromo-2-phenyloxazole.
b. Nitration & Sulphonation: Nitration and Sulphonation of Oxazole itself are
difficult.
N
O C6H5
NBS N
O C6H5
Br
2- Phenyloxazole 5- bromo- 2-phenyloxazole
N
O
HNO3
H2SO4
N
O
NO2
2- Phenyloxazole
N
O
N
O
SO3H
2- Phenyloxazole
H2SO4
Oleum
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7. 3. Nucleophilic substitution
Oxazole do not undergo nucleophilic substitution reactions. Oxazole ring cleaves
frequently rather than substitution with nucleophilic reagents. Sometimes the cleaved ring may
be cyclised.
4. Oxidation: Oxazole ring system is cleaved by oxidizing agents (KMnO4, H2CrO4, O3),
however it is stable with H2O2.
N
O CH3
H5C6
H5C6
2-methyl- 4, 5-diphenyloxazole
NH3
N
H5C6
H5C6
O
CH3
N
H2
Cyclisation N
N
H
CH3
H5C6
H5C6
2- methyl- 4, 5 -dimethylimidazole
N
O C6H5
H5C6
H5C6
2, 4, 5-triphenyloxazole
[O]
COOH
3
Benzoic acid
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8. 5. Reduction
Oxazoles are stable in the presence of reducing agents. However, they can be
reduced to Oxazolidines with sodium in ethanol.
6. Diel’s-Alder Reaction
Oxazole behave as dienophiles and forms an adduct by undergoing Diel’s Alder
reaction with a diene or alkyne.
N
O
Na - C2H5OH N
O
Na - C2H5OH NH
O
Ozazole
Oxazoline Oxazolidine
N
O R"
R
R'
+
COOCH 3
COOCH 3 N R"
COOCH 3
COOH
R
R'
Dienophile Diene Adduct
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10. Trimethadione
Trimethadione is an anti-epileptic medication,
also called an anticonvulsant.
Paramethadione
Paramethadione is an anticonvulsant drug
N
O O
CH3
O
H3C
H3C
Trimethadione
N
O O
CH3
O
H3C
H5C2
Paramethadione
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11. Ditazole
Ditazole is a non-steroidal anti-inflammatory drug (NSAID).
Additionally, ditazole is a platelet aggregation inhibitor.
Furazolidone
Furazolidone is used for the specific and symptomatic
treatment of bacterial or protozoal diarrhoea and enteritis
caused by susceptible organisms.
N
O N
H5C6
CH2CH2OH
CH2CH2OH
H5C6
Ditazole
N
O
N O
O
NO2
Furazolidone
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12. Metaxalone
Metaxalone is a muscle relaxant medication used
to relax muscles and relieve pain caused by strains,
sprains, and other musculoskeletal conditions.
Toloxatone
For the treatment of major depressive disorder
NH
O O
O
CH3
H3C
Metaxalone
N
O O
HOH 2C
CH3
Toloxatone
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